The isolated perfused rat liver will be utilized to study the catabolism of radio-iodinated insulin glucagon and growth hormone. Following perfusion at varying times and temperatures with the radioiodinated hormone, the livers will be homogenized and subcellular fractions prepared by differential centrifugation for determination of distribution of radioactivity. The mitochondrial-lysosomal (M+L) subfraction will be subjected to sucrose density gradient centrifugation and to separation on a Ludox-polyvinylpyrrolidone-sucrose gradient for isolation of the lysosomal fraction. The specific aims of the study are to investigate the mechanisms by which the liver catabolizes peptide hormones to quantitate the role lysosomes play in this catabolism and to utilize the purified lysosomes for the study of biochemical and physical characteristics of lysosomes.